Evidence map›Paper›PMID 16568090›Full record

ArticleOncogene2006

Oncogenic HRAS suppresses clusterin expression through promoter hypermethylation.

P Lund, K Weisshaupt, T Mikeska, D Jammas, X Chen, R-J Kuban, U Ungethüm, U Krapfenbauer, H-P Herzel, R Schäfer and 2 more

Abstract read
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In one paragraph

Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 69 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

P LundLaboratory of Molecular Tumor Pathology, Institute of Pathology, Charité, Berlin, Germany.
K Weisshaupt
T Mikeska
D Jammas
X Chen
R-J Kuban
U Ungethüm
U Krapfenbauer
H-P Herzel
R Schäfer
J Walter
C Sers
Charité - Universitätsmedizin Berlin · DESaarland University · DEHumboldt-Universität zu Berlin · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Silencing of gene expression by methylation of CpG islands in regulatory elements is frequently observed in cancer. However, an influence of the most common oncogenic signalling pathways onto DNA methylation has not yet been investigated thoroughly. To address this issue, we identified genes suppressed in HRAS-transformed rat fibroblasts but upregulated after treatment with the demethylating agent 5-Aza-2-deoxycytidine and with the MEK1,2 inhibitor U0126. Analysis of gene expression by microarray and Northern blot analysis revealed the MEK/ERK target genes clusterin, matrix metalloproteinase 2 (Mmp2), peptidylpropyl isomerase C-associated protein, syndecan 4, Timp2 and Thbs1 to be repressed in the HRAS-transformed FE-8 cells in a MEK/ERK- and methylation-dependent manner. Hypermethylation of putative regulatory elements in HRAS-transformed cells as compared to immortalized fibroblasts was detected within a CpG island 14.5 kb upstream of clusterin, within the clusterin promoter and within a CpG island of the Mmp2 promoter by bisulphite sequencing. Furthermore, hypermethylation of the clusterin promoter was observed 10 days after induction of HRAS in immortalized rat fibroblasts and a clear correlation between reduced clusterin expression and hypermethlyation could also be observed in distinct rat tissues. These results suggest that silencing of individual genes by DNA methylation is controlled by oncogenic signalling pathways, yet the mechanisms responsible for initial target gene suppression are variable.

Indexed as

DNA MethylationGenes, rasGenes, SuppressorPromoter Regions, GeneticAnimalsAntimetabolites, AntineoplasticApoptosisAzacitidineCell Line, TransformedClusterinDecitabineHydroxamic AcidsRatsSignal TransductionAntimetabolites, AntineoplasticAzacitidineClu protein, ratClusterinDecitabineHydroxamic Acidstrichostatin A

Identifiers

PMID16568090
OpenAlexW1998262721

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.